Liver and Intestinal Organ Transplantation Committee

Update on Liver Allocation and DistributionACOT

August 28, 2012

Kim M. Olthoff, MD, ChairDavid C. Mulligan, MD, Vice-ChairAnn Harper, UNOS/OPTN Liaison

Allocation: Allocate: “to apportion for a specific purpose or to

particular persons or things” –merriam-webster.com

Current liver allocation is based upon the “sickest first” principle Uses MELD allocation system Allows for standard and non-standard exceptions

Alternative allocation models Transplant benefit Variations on MELD (ie MELD-Na)

Liver allocation and distribution

Distribution: Distribution: “the position, arrangement, or frequency

of occurrence (as of the members of a group) over an area or throughout a space”

–merriam-webster.com

Current liver distribution is based mostly upon “local first” principle Broader sharing for high status and pediatrics

Alternative distribution models Concentric circles Population based

Liver allocation and distribution

2/27/2002: MELD /PELD Implemented

01/15/2005: “Share 15 Regional”

08/15/2005: Revised Status 1 and broader sharing for pediatric donor (age 0-17)

11/18/2010: Broader sharing of pediatric LIs and LI-INs from 0-10 yr old donors

12/15/2010: Regional sharing for Status 1s

MELD/PELD historical timeline

1. Combined OPO and Regional LI Status 1A 2. Combined OPO and Regional LI Status 1B3. OPO LI MELD/PELD ≥ 154. Regional LI MELD/PELD ≥ 155. OPO LI MELD/PELD < 156. Regional LI MELD/PELD < 157. National LI Status 1A8. National LI Status 1B9. National LI MELD/PELD >=15

National LI MELD/PELD <15

Current Algorithm*

*Does not include recently-approved liver-intestine policy

• Despite improvements in liver allocation and distribution, waitlist mortality remains high for patients with higher MELD scores

• Significant disparity exists between OPOs and regions with regard to mean MELD at transplant and waitlist mortality

• How can we start to correct this problem?

Problem Statement

13.6

55.5 62.8

8.8

17.4

33.7

6.9

5.3

70.7

21.8

0%10%20%30%40%50%60%70%80%90%

100%

< 15 15-34 35+MELD Category at Listing

Still WaitingOther RemovalDeathTransplant

Competing Risk Liver Waiting List Outcome Probabilities at 1-YearCandidates Added 2007-2010

*Status 1A/1B, and candidates with exceptions excluded

N=10319 N=15810 N=2363

0

5

10

15

20

25

30

35

40

1 2 3 4 5 6 7 8 9 10 11

Mea

n M

/P @

Tra

nspl

ant

Region

Mean Match MELD @ Transplant* Deceased Donor Liver Transplants, 2010 by DSA within Region

*Adults only, Exceptions. Some DSAs may overlap

0%

5%

10%

15%

20%

25%

30%

35%

1 2 3 4 5 6 7 8 9 10 11

% D

ied

at 1

yea

r

Region

Death Rates* @ 365 Days, Candidates Listed for a DD Liver Transplant 1/1/2008-12/31/09By DSA within Region

*Adults only, Calculated using Competing Risks, Exceptions, Initial MELD>=15, Candidates with an Initial Status of 1A/1B Excluded, DSAs with fewer than 10 events excluded

• Proposal for Regional Sharing (February 2009)

• Request for Forum (June 2009)

• RFI and Survey (December 2009)

• Forum in Atlanta (April 2010)

• Board directed Committee “to develop recommendations to reduce geographic disparities in waitlist mortality” (June 2010)

• Concept Paper/Survey (December 2010)

Policy Development History I

• Presentations at AASLD, ASTS Winter Symposium, ATC (2010 and 2011)

• Public Comment (September - December 2011)

• Public Webinar (October 2011)

• Review of Comments (March 2012)

• Final Committee Vote (May 2012)

Policy Development History II

• Full Regional Sharing – strong opposition

• Concentric Circles – mixed support

• Extension of Share 15 Regional – strong support

• Tiered Regional Sharing – strong support for some level (29, 32, 35, other)

• Net Transplant Benefit – mixed support

Options Considered

Further SRTR modeling and analysis of death rates and post transplant outcomes in high MELD patients

Fall 2011- Proposal for public comment for regional sharing for high MELD patients and national sharing for MELD >15 prior to local/regional MELD <15

Addressed issues from public response with further analysis MELD exceptions Combined LK transplants

Proposal submitted to OPTN BOD June 2012 National Share 15 Regional Share 35

LIC Plan of action

Results: Waitlist Mortality – Intent to treat

MELD35+ 1A MELD35+ 1A7 Days Follow-up 30 days Follow-up

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

12.3

14.5 26

.9

17.5

32.1

54.7

55.2

59.1

55.5

30.8 17

.9

23.5

Censor

Transplant

Death

Results: Waitlist Mortality – Intent to treat

0 5 10 15 20 25 300.00

0.01

0.02

0.03

0.04

0.05

1AMELD 35+

Time from onset of the Status (Days)

Deat

h Ra

te (D

eath

per

Day

)

50 60 70 80 900

20

40

60

80

Decrease in Total Deaths vs. Median DistanceCurrent

R35_Current

Share 15 National

R35_S15National

Median distance (nautical miles)

Dec

reas

e in

tota

l dea

ths

Share 15 National

Current

R35 w/ S15N

R35 w/Current

MELD/PELD 35+ Candidates 2009 – 2011: By Region

Candidates Reaching M/P 35+ AllNo YesN % N % N

Region2313 87.6 326 12.4 26391

2 5695 87.0 849 13.0 65443 4586 91.1 446 8.9 50324 6022 91.4 566 8.6 65885 8725 85.1 1527 14.9 102526 1062 91.2 103 8.8 11657 3726 85.3 644 14.7 43708 3019 91.8 268 8.2 32879 3954 90.5 415 9.5 4369

10 3065 90.4 326 9.6 339111 3632 93.6 248 6.4 3880All 45799 88.9 5718 11.1 51517

The percentage of all candidates listed who entered MP35+ ranged by region from 6.4% to 14.9%. Regions 2,5 and 7 had the largest numbers.

MELD/PELD 35+ Candidates 2009 –2011: Categories of Exceptions and Standard Cases

MP35 Category N %

HAT Exception 121 2.12

HCC Exception 36 0.63

Liver-Intestine 141 2.47

Other Exception 275 4.83Standard MELD/CRRT(HD 2x in week) 1631 28.52

Standard MELD/no CRRT 3514 61.46

Total 5718 100.00

About 90% of the candidates in MP35+ were assigned standard MELD/PELD scores; less than 1% were HCC exceptions.

Death 30 days

Death 90 days

Transplant 30 days

Transplant 90 days

0

10

20

30

40

50

60

70

28.4

36.4

44.8

52.7

27.630.9

54.960.1

32.537.4

52.256.6

25.629.1

54.560.5

On KI WL Not on KI WL On Dialysis Not on Dialysis

% D

ied

or T

rans

plan

ted

MELD/PELD 35+ Candidates 2009 –2011: Rates of Death* and Transplant By Kidney Listing/Dialysis

*Includes candidates removed for too sick

Being either on the KI WL or on dialysis was associated with higher death rates and lower transplant rates. Candidates on KI WL and on dialysis (N=430) had highest death rates at 90 days (39.1%) and lowest transplant rate (49.8%) (data not shown).

Hypothesis: Greater access to organs for sicker candidates will decrease their waiting list mortality, without a demonstrable increase in mortality for other candidates, due to the small number of candidates involved.

• Extension of Regional Share 15 => Share 15 National

• Share 35 Regional - Candidates with MELD/PELD scores of 35 and higher

Policy Changes Proposed at Spring 2012 UNOS/OPTN BOD meeting

1. Regional Status 1A2. Regional Status 1B3. Local MELD/PELD>=154. Regional MELD/PELD>=155. National Status 1A6. National Status 1B7. National MELD/PELD>=158. Local MELD/PELD<159. Regional MELD/PELD<1510. National MELD/PELD<15

Share 15 National*

* Adult Donors Only

1. Regional Status 1A2. Regional Status 1B3. Local and Regional M/P >=354. Local M/P 15-345. Regional M/P 15-346. National Status 1A7. National Status 1B8. National M/P ≥ 159. Local M/P < 1510.Regional M/P <1511.National M/P < 15

Share 35R, Combined with Share 15N*3.1 Local M/P 403.2 Regional 403.3 Local M/P 393.4 Regional M/P 393.5 Local M/P 383.6 Regional M/P 383.7 Local M/P 373.8 Regional M/P 373.9 Local M/P 363.10 Regional M/P 363.11 Local M/P 353.12 Regional M/P 35

* Adult Donors Only

Passed by the UNOS/OPTN BOD June 2012Implementation dates depend upon Chrysalis

Data to be reviewed every 6 months :

•Waiting list mortality by MELD score

• Post-transplant patient and graft survival

• Percent shared between OPOs

• Percent shared nationally

• Percent of MELD exceptions scores transplanted at high MELDs (35+)

Plan for evaluation after implementation

HCC patients get transplanted sooner than non-HCC patients

HCC patients have lower dropout rate than non-HCC patients across all regions

MELD, AFP and tumor size are predictors of dropout, but non-HCC still has higher drop-out

Future allocation initiatives:HCC Exceptions

1 2 3 4 5 6 7 8 9 10 11 US0

5

10

15

20

25

30

HCC

Non-HCC (MELD < 21)

Non-HCC (All)

Region

% D

ropo

ut% Dropout within 12 Months: HCC and Non-HCC Candidates by Region

Transplant rates and death rates vary markedly across regions, particularly at MELD scores > 15

HRSA has asked SRTR to pursue a redistricting project focused on reducing geographic disparities in liver distribution. Liver committee determines principles of allocation (like reducing disparities,

reducing waitlist death, offering to highest MELD candidates) and limits of transport times

Mathematical redistricting to design optimal regions based on these principles (Principles-Based Optimization)

Improvements to inference: transport time estimates to understand geographic limits of broader sharing; LSAM upgrades

Future Distribution Initiatives:Re-imagining distribution units

Transplant rates across OPOs

MELD 38-39: 18% to 86%

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

Geography and Design Engineering

Principles-Based Optimization Important to agree on the framework up front

Keep current OPOs intact? How many regions? How compact should the regions be? Contiguous? What is the metric we are trying to optimize?

(Decrease pre-transplant deaths?)(Reduce variance in MELD at transplant?)

How do we balance tradeoffs?

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

Optimized redistricting

We regroup existing DSAs into novel regions using an integer programming model.

The model assigns each DSA to exactly one region, and includes constraints to ensure that the MELD level at which any region exhausts its supply of livers is similar across regions.

The model minimizes the sum of the squared distances between all the DSAs and the location of each region.

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

Optimized Map 1

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

Optimized Map 2

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

Optimal maps reduce variance

4.3 4.6 2.5 2.5

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

Transport time and cold ischemia

Presented to OPTN BOD June 2012 by D. Segev and S. Gentry

• Cold ischemic time only weakly correlated with distance traveled

• Distance is not a proxy for travel time

Goal: Minimize disparity Improve and maximize outcome

Final rule: “Neither place of residence nor place of listing shall

be a major determinant of access to a transplant.”